[in Japanese]

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Isolated bacteria from infections in general surgery in 1984 and 1985 have been investigated to find bacterial composition and their susceptibilities to antibiotics in a joint research in which 6 university hospitals in Japan participated. A summary of findings from the investigation is as follows.
1. One hundred and seventy-two (1984) and 211 (1985) cases were included in the study. Cases in which bacteria were detected were 147 and 174 in the respective years. The detection rate was higher than 80% in either year.
2. Total numbers of strains isolated in 1984 and 1985 were 267 and 293, respectively; major source of these strains were intraperitoneal infection exudates in either year.
3. The most frequent isolate from primary infection cases in both years was Escherichia coli (15-21%), followed by Bacteroides spp. and Staphylococcus spp., in that order. The most frequently isolated from postoperative infection cases were Enterococcus spp.(16-22%), followed by Pseudomonas spp. The diversity of isolated species, as well as the similarlity of incidences of different species were noted in cases of postoperative infections. It is suspected that a certain species, even if its pathogenicity is essentially low, may become to be a causative organism once its number increases due to its survival through a perioperative prophylactic use of antibiotics, and also due to the decreased host resistance to infections caused by underlying diseases or surgical stress.
4. Staphylococcus spp. was the most frequent isolate from postoperative infections occuring after clean operations, while Enterococcus spp. and Pseudomonas aeruginosa were major isolates from infections after clean-contaminated operations. Isolates from infections occuring after con taminated operations included Enterococcus spp. >E. coli>Klebsiella pneumoniae, P. aeruginosa, Bacteroides spp.(1985).
5. In cases without the presence of clinical factors cause by depressed host defense, E. coli and Bacteroides spp. were major isolates, while in cases with the factors, a wide variety of bacterial population tended to be found.
6. Before an administration of antibiotics in primary infections, E. coli, Staphylococcus spp. Bacteroides spp. and Klebsiella spp. were most commonly isolated, while after a chemotherapy, Enterococcus spp. were the most frequent isolates, followed by P. aeruginosa during 1985. These findings reflected the antibacterial spectrum of cephems usually used in surgical field.
7. Frequencies of isolates during the 4 years from 1982 to 1985 did not reveal significant changes in the populations of Gram-positive group, although they showed a small decrease in Gram-negative group and a small increase in anaerobic bacteria.
8. Changes in drug-susceptibilities of bacteria to 14 antibiotics during the 4 years from 1982 to 1985 were studied using 6 bacterial species (Staphylococcus aureus, Enterococcus faecalis, E. coli, K. pneumoniae, P. aeruginosa and Bacteroides fragilis). Fluctuations of MIC₈₀ values for all species except P. aeruginosa were small and there was no significant increase in numbers resistant strains. MIC₈₀'s of these antibiotics but amikacin for P. aeruginosa showed that a wide variation occurred during the 4 years, suggesting that highly resistant strains may pos-sibly be increasing.
We did not investigate methicillin resistant S. aureus in the present study, but, considering from a decreasing trend observed in susceptibilities of S. aureus to cefazolin or aminoglycosides during our study, detailed investigations should be performed in the future.

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A monotherapy of aztreonam (AZT) was applied to 9 male and 3 female pediatric patients of ages ranging from 2 months to 8 years and 11 months with serious purulent meningitis. The results are summarized as follows:
1. Daily dosages of 134 to 400mg/kg were given 3 to 4 times a day for 10 to 28 days.
2. The isolated pathogens were Neisseria meningitidis in 2 cases, Escherichia coil in 3 cases, Haemophilus influenzae in 6 cases, but the pathogen of the last case was unknown. In this case, the patient had myelomeningocele and suffered from recurrent purulent meningitis.
3. Clinical effect was “excellent” in 5 of 12 cases, “good” in 7 cases and efficacy rate was 100%. Microbiological tests were performed on 9 cases during the course of treatment and bacterial elimination rate was 100%. All the pathogens were eliminated in 72 hours.
4. One case of diarrhea was observed, but the diarrhea started before the administration. of AZT and was stopped after the AZT treatment. A slight elevation of GOT value was observed in 1 case but the value returned to the initial level promptly after the treatment was completed.
It is considered that AZT is highly useful for purulent meningitis caused by Gram-negative pathogens such as H. influenzae, E. coli and N. meningitidis.

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As one of our clinical studies on per rectal administration of antibiotics, children who suffered respiratory tract infection (RTI) were administered with ampicillin (ABPC) through this route.
Our conclusions drawn from this study are as follows:
1. One hundred and eighty strains of aerobic bacteria which were isolated by us in 1984-1985 were tested for the sensitivity to ABPC using plate-disk method. MIC's of ABPC for all the strains of Streptococcus pyogenes were lower than 0.024μg/ml. MIC's for all the strains of Streptococcus haemolyticus were 0.05-0.20μg/ml. MIC's for 88% of the strains tested of Haemophilus influenzae were0.10-0.78μg/ml.
2. Bacterial flora in the respiratory tract of 97 cases of children, who suffered RTI, were cultured. Almost half of them were Gram-positive cocci, the rest belonged to Gram-negative groups. This indicates that broad-spectrum antibiotics should be chosen first even before the diagnosis of causative organisms is established.
3. Soon after a per rectal administration of ABPC to children, high blood concentrations of the drug were observed by paper-disk method.
4. Eleven cases, which included 2 cases of pneumonia, of 15 children who suffered RTI and were given this antibiotic were greatly improved within 3-10 days. No serious side effects were observed.
5. Our brief study reported here indicates that ABPC administration by rectal route is safe and useful for the clinical treatment of RTI of children.

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The pharmacokinetics of cefotiam (CTM) was investigated in 7 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). One gram of CTM was infused either intravenously (i. v. group) or intraperitoneally (i. p. group).
In the i. v. group, the serum concentration of CTM at 6 hours after infusion was 25.9 mg/L and the half-life value was 5.09 hours, while the peak value of CTM in dialysate was 12.4 mg/L.
In the i. p. group without peritonitis, the dialysate concentration of CTM at 6 hours after infusion was 108.6 mg/L. The serum concentration at 15 minutes after infusion was 3.0 mg/L, the corresponding peak value was 14.0 mg/L at 4 and 6 hours after infusion.

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Cefoperazone (CPZ) was administered to 10 patients with cerebrovascular disturbances at acute and chronic phases to investigate its passage into the cerebrospinal fluid. The antibiotic was administered at dosages of 1g and 2g to patients in the acute phase to examine the dose-dependency. The results obtained are summarized as follows:
1. Serum concentrations
Peak values of CPZ were 46.9±4.42μg/ml in acute phase patients in 1g dosage group (acute group 1), 253.1±63.2μg/ml in acute phase patients in 2g dosage group (acute group2), and 197.9 ±15.7μg/ml in, chronic phase patients in 2g dosage group (chronic group 2) at 1 hour after CPZ administration.
Concentrations of CPZ varied about 5-fold between the 1g dosage group and the 2g dosage groups. The acute group 2 showed generally higher values of CPZ concentrations than the chronic group 2,
2. Cerebrospinal fluid concentrations
Peak values Were 0.96±0.30μg/ml (at 3 hours) in acute group 1, 4.55±3.41μg/ml (at 1 hour, except 1 case) in acute group 2, and 1.29±1.28μg/ml (at 1 hour) in chronic group 2.
Acute group 2 showed generally higher values than chronic group 2.
3. CPZ Was considered useful for the prevention of postoperative infections in the field of brain surgery.

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Seventy five patients with respiratory infections, including 40 cases of acute pneumonia, 33 cases of secondary infection after chronic pulmonary diseases and 2 cases of pulmonary abscess, were treated with cefotetan (CTT, Yamatetan ^®;) by drip infusion in order to evaluate its clinical efficacy. The overall rate of effectiveness was 83.8%.
CTT was examined comparatively with other beta-lactam antibiotics for antibacterial activity on clinically isolated strains of 3 major respiratory pathogens including Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae. Minimum inhibitory concentrations (MIC's) of CTT on H. influenzae were less than 3.13μg/ml regardless of the production of beta-lactamase by these organisms. As to B. catarrhalis, CTT also exerted an antibacterial activity enough to control the proliferation of all the strains at a level of 1.56μg/ml. Against S. pneumoniae, on the other hand, CTT exhibited the lowest activity of all the drugs tested but still showed MIC's of 3.13μg/ml or less.
Drip infusion of CTT at a dose of 2g brought about an average maximum blood concentration of 342μ25.7μg/ml and an average half-life in blood of 2.48μ0.41 hours Maximum sputum concentration of the drug, however, was variable among the cases tested, ranging from 0.40 to 1.80μg/ml.
Side effects of the drug were observed in 5 cases or 6.7%. Four of them had some allergic symptoms; i. e., pyrexia and eruption. One patient was especially diagnosed as possible druginduced interstitial pneumonia during the treatment with the drug. The diagnosis was confirmed by transbronchial lung biopsy and lymphocyte blastogenesis by CTT in vitro. As to abnormal laboratory findings, blood transaminases were elevated during drug administration in 13 cases or 17.3%, but were reduced back to the normal level after the withdrawal of the drug

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In an attempt to clarify the role of a side chain, N⁴-methyl-D-asparagine, of aspoxicillin (ASPC) in the antibacterial action, we examined the bactericidal activity of dehydroxyaspoxicillin (AB-ASPC) and its affinity for the penicillin-binding proteins (PBPs) of Escherichia coli using piperacillin (PIPC), mezlocillin (MZPC) and apalcillin (APPC) as the reference penicillins.
ASPC and AB-ASPC showed high bactericidal activities against E. coli K-12 even when a large inoculum size (2×10⁸CFU/ml) was used. The observation of these cultures with a phase contrast microscope revealed that E. coli cells lysed after the formation of spheroplast-like or bulged structures. On the other hand, PIPC, MZPC and APPC converted the cells to long filaments, but did not show lytic action in the range of the concentrations used. These morphological changes were also observed with a scanning electron microscope.
Superior bacteriolytic activities of ASPC and AB-ASPC were further shown by measuring ×triggering autolytic activity by the penicillins. The release of labeled murein from E. coli χ1776 after the exposure to ASPC or AB-ASPC was clearly greater than those caused by reference penicillins.
ASPC showed affinity for PBPs of E. coli K-12, 1A, 1Bs, 2 and 3, and its affinity pattern resembled the one obtained with ampicillin (ABPC). AB-ASPC behaved in a fashion similar to ASPC, although its affinities for PBP 1A and 1Bs were lower and that for PBP 3 was slightly higher.
These observations suggest that the highest bactericidal activity of ASPC against E. coli with lysis among the acyl-ureidopenicillins tested is due to N⁴-methyl-D-asparagine in the side chain of ASPC.

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The following findings were obtained in our clinical study on the transfer of cefotetan (CTT) and cefbuperazone (CBPZ), new antibiotics of cephamycin series, into the lung tissue and on their postoperative prophylactic effect.
1. The mean serum concentration 30 minutes after the start of an intravenous drip infusion of 1g of CTT over a period of 30minutes was 99.4μg/ml, and it decreased gradually thereafter with the half-life of 2.45 hours. After an intravenous drip infusion of 1g of CTT over a period of 1hour, the mean peak concentration of 104.1μg/ml appeared 1hour after the start of the infusion, and mean concentrations at 2, 4 and 6 hours after the infusion were 63.4, 34.3 and 27.0 g/ml, respectively, with the half-life of 2.35 hours during phase β
2. Following 30 minutes of an intravenous drip infusion of CTT, the tissue CTT level in normal lung tissues was T_max 1.82 hours and C_max 19.8μg/g. After 1 hour of an intravenous drip infusion the mean concentration in the tissues was at the peak of 39.7μg/g in 2 hours after the start of an administration, while mean levels at 3, 4 and 6 hours after an administration were 32.2, 22.2 and 8.76μg/g, respectively, with T. of 1.82 hours and C_max of 30.5μg/g.
3. Following an intravenous drip infusion of 1 g of CBPZ over a period of 1 hour, the mean serum drug concentration 1 hour after the start of infusion was at its peak, 83.3μg/ml, while mean values at 2, 4 and 6 hours after the start of an administration were, respectively, 40.4, 19.8 and 9.62μg/ml, with the β-phase half-life of 2.03 hours.
4. By 1 hour after the start of intravenous drip infusion of CBPZ, the mean tissue level in normal lung tissues was at the peak of 31.6μg/g, while mean levels at 3, 4 and 8 hours after an administration were 16.2, 11.0 and 4.56μg/g, respectively, with T_max of 1.67 hours and C_max of 21.9μg/g.
5. Infused CBPZ was transferred into bronchiole tissues. Drug concentrations in these tissues at 3 and 5 hours after the start of the infusion were 7.87 and 4.85μg/g, respectively, with their ratios to the peak serum level were 9.4 and 5.8%, respectively.
6. CBPZ was similarly transferred into the hilar lymph nodes and mean drug concentrations at 2, 3, 3, 5, 4 and 5 hours after the start of the infusion were 7.49, 5.96, 10.2, 7.63 and 3.52μg/g, respectively, with T_max of 2.23 hours and C_max of 7.93μg/g.
7. Postoperative infections did not occur in the CTT-and CBPZ-treated patients with the exception of one CBPZ administered case in which esophageal fistula of unknown etiology leading to pyothorax occurred. No severe side effect of the drugs appeared in any of the treated patients, and both drugs were useful in the prevention of postoperative infections in the patients with respiratory diseases.

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Cefbuperazone (CBPZ) at a dose of 2g was administered postoperatively by intravenous drip infusion to 9 patients subjected to radical mastectomy and 10 others subjected to thyroidectomy then levels of CBPZ in postoperative exudates were measured and its prophylactic effect on postoperative infections was determined.
1. Serum CBPZ levels in the patients after cancer mastectomy and thyroidectomy on postoperative day 1 were similar to those in healthy adults.
2. Levels of CBPZ in the postoperative exudates in patients subjected to cancer mastectomy reached a mean peak value of 66.3μg/ml (range: 26.0-99.6μg/ml) in 0-3 hours after administration, and the mean CBPZ level at 6 hours after administration was 33.3μg/ml (range: 19.1-54.1μg/ml).
3. As compared to the cases of cancer mastectomy, levels of CBPZ in postoperative exudates in patients subjected to thyroidectomy varied considerably from a patient to another: a mean peak level of 76.4μg/ml (range: 31.3-128μg/ml) appeared in 0 to 6 hours after administration.
4. There was no correlation between CBPZ levels in the exudate and hemoglobin levels or hematocrit values.
5. Likely because of the CBPZ administration at 4g/day for 2 to 6 days postoperatively to 19 patients, postoperative infection was absent and no side effect attributable to this drug occurred in any of the patients.
Because levels of CBPZ in postoperative exudates in patients subjected to cancer mastectomy or thyroidectomy were greater than MICs for principal Gram-positive and Gram-negative bacteria, it is likely that this drug is a useful agent for prophylaxis against postoperative infections in patients undergoing cancer mastectomy or thyroidectomy.

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